Pharmacology Review: Sodium Phenylacetate and Sodium Benzoate in the Treatment of Neonatal Hyperammonemia

Abstract

Ammonia is present in all body fluids and exists primarily as ammonium ion at physiologic pH. Hyperammonemia is defined as a blood ammonia concentration greater than about 100 mcmol/L in neonates or 50 mcmol/L in children and adults (precise cut-offs vary, depending on individual laboratory normative ranges). The concentration of ammonia is 10 times higher in tissue than in blood. A 5- to 10-fold increase in blood ammonia concentration usually is toxic to the nervous system. Hyperammonemia in the neonatal period, especially when due to inborn errors of metabolism, can progress rapidly and cause severe neurologic damage or early death. Hyperammonemia can be caused by inborn errors of metabolism as well as by a variety of acquired conditions (Tables 1 and 2). Urgent treatment is required because of the potential for irreversible neurologic sequelae that can, in many cases, be prevented by prompt diagnosis and institution of therapy. | Urea cycle defects | || | Amino acid transporter deficiencies | | Organic acidemias | | Fatty acid oxidation defects | | Pyruvate carboxylase deficiency | | Mitochondrial disorders | | Hyperinsulinism/hyperammonemia syndrome (glutamate dehydrogenase mutations) | | Delta1-pyrroline-5-carboxylate synthase deficiency | Table 1. Inborn Errors of Metabolism Associated With Hyperammonemia | Sampling artifact | || | Cardiovascular | | Perinatal asphyxia | | Liver failure | | Bacterial colonization (urease-positive organisms) | | Iatrogenic | Table 2. Causes of Acquired Hyperammonemia The combination of sodium phenylacetate (NAPA) and sodium benzoate (NABZ) in a 10%/10% solution is an intravenously administered United States Food and Drug Administration (FDA)-approved drug used as adjunctive therapy for …